This invention relates to an antibacterial-containing oral composition which promotes oral hygiene, controls plaque formation, gingivitis and periodontitis, by the topical application to the oral cavity, of a mouthrinse or dentifrice containing an effective amount of the antigingivitis agent, 1-imidazoyl-1-(p-chlorophenoxy) 3,3-dimethyl 2 -butanone (Climbazole by Bayer).
Periodontitis, or pyorrhea, is a disease affecting the supporting tissues of the teeth including the gingiva, the membrane lining the sockets in which the teeth lie, and the bones surrounding the teeth. The disease may initially be associated with conditions of constant irritation of the gingiva by dental plaque, food impaction, poor dental restorations, traumatic occlusion, or chemical irritants.
The gums may be seriously harmed by deposits of dental plaque, a combination of minerals and bacteria found in the mouth. The bacteria associated with plaque can secrete enzymes and endotoxins which can irritate the gums and cause an inflammatory gingivitis. As the gums become increasingly irritated by this process they have a tendency to bleed, lose their toughness and resiliency, and separate from the teeth, leaving periodontal pockets in which debris, secretions, more bacteria and toxins further accumulate. It is also possible for food to accumulate in these pockets, thereby providing nourishment for increased growth of bacteria and production of endotoxins and destructive enzymes. The pus that forms in this process is capable of destroying gum and bone tissue. Bacteria are generally found to be present during the active stages of periodontal disease. Such organisms as anaerobic gram negatives are usually present, and are found in the purulent discharge as well as in the involved tissue, and may be absorbed into the general system through the lymphatics or venous blood stream.
The progression of the pyorrheic process usually begins with gingivitis, initiating at the margins of the gums, in which the gingiva become more tender and sensitive, and appear flabby, inflamed and swollen. Periodontal pockets become apparent, and infection takes place in these pockets. Effective control and prevention of gingivitis accordingly constitutes a desideratum for the prevention of further periodontal diseases.
A multitude of materials have been previously proposed and employed for controlling oral disease and malfunctions such as plaque, calculus, tartar, caries, halitosis, and periodontal diseases such as gingivitis and pyorrhea, but none have been entirely satisfactory. For example, oral compositions containing anti-inflammatory agents which reduce the symptoms of swelling, bleeding and inflammation associated with gingivitis, by preventing tartar formation and/or countering oral calculus, include an imidazole such as histadine or histamine as disclosed in U.S. Pat. No. 3,497,591; a dichloro-2-guanidino benzimidazole, as disclosed in U.S. Pat. No. 3,523,154; carragheenin as disclosed in U.S. Pat. No. 4,029,760; a mixture of tranexamic acid and folic acid, as disclosed in U.S. Pat. No. 4,272,512; and tannic acid, as disclosed in U.S. Pat. No. 4,273,758. All of aforesaid agents are non-antimicrobial.
U.S. Pat. No. 3,577,520 also discloses a dentifrice composition containing 5,5-diaryl-2,4-imidazolidinediones in the treatment of pyorrhea, by repairing the lesions of paradontosis.
U.S. Pat. No. 3,911,133 discloses an antibacterial composition effective against both gram positive and gram negative bacteria, comprising an imidazole derivative, which is a bis(imidazolium quaternary salt), useful in mouthwashes, toothpastes and dental gels as a method of inhibiting the formation of dental plaque or in the prevention of gingivitis.
U.S. Pat. No. 4,243,670 discloses imidazolium derivatives having strong antimicrobial activity against dermatophytes, yeasts, molds, biphase fungi and gram positive cocci; and useful as an additive to oral hygiene products such as toothpastes and mouthwashes, to avoid microbially caused infections of the mucosa of the mouth and as a prophylactic against infection.
It is also known in the art, that certain gram negative organisms such as Bacteriodes asaccharolyticus or Bacteriodes gingivalis are associated with adult periodontitis. By eliminating these and other gram negative anaerobes from the plaque accumulated on the gingival tissues, effective control and prevention of periodontal disease can be achieved.
Accordingly, it has been shown by Listgarton et al in the J. Periodont. Res. 14: 65-75 (1979), that metronidazole, ##STR1## given systemically causes the elimination of said gram negative anaerobes from the plaque. This was substantiated by Heijl and Lindhe in the J. Clinical Periodontology 6, 197-209 (1979), wherein is shown that metronidazole is effective in reducing plaque and gingivitis scores in dogs; and by Loesche et al in the J. of Clinical Periodontology, 8: 29-44 (1981), wherein it is shown that metronidazole is effective in reducing the anaerobic B. asaccharolyticus count in plaque removed from periodontal pockets, concommitantly, with a substantial reduction in pocket depth and considerable gain in apparent attachment. However, metronidazole, sold under the tradename of Flagyl, is carcinogenic (Physician Reference Handbook p. 1761) and cannot be used indiscriminately.
It has now been found that another derivative of imidazole is effective against said gram negative anaerobic organisms, which is nonmutagenic, noncarcinogenic and can be topically applied to the oral cavity in the treatment of gingivitis, namely, 1-imidazoyl-1-(p-chlorophenoxy)3,3-dimethyl 2-butanone.
The imidazoyl ketones such as 1-imidazoyl-1-(4-chlorophenoxy)-3,3-dimethyl 2-butanone, are disclosed in U.S. Pat. Nos. 3,812,142 and 3,903,287 as an anti-mycotic agent, useful in pharmaceutical compositions including pastes, gels, creams, aqueous and nonaqueous suspensions. Its action against pathogenic protozoa, gram positive and negative bacteria such as Staphlococci and Escherichia coli is also noted therein. British Pat. No. 1,502,144 and its German counterpart, Pat. No. 2,430,039, disclose hair or skin treating compositions, effective against Pityrosporum ovale, containing the imidazolyl ketone antimycotic agents dispersed in a dermatologically acceptable carrier which contains a detergent-active compound. These compositions are in the form of creams, aerosols, powders and liquids. German Pat. No. 2,600,800 discloses the 1-imidazoyl-1-(4-chlorophenoxy)-3,3-dimethyl 2-butanone in a fungicidal composition, either in dry form, as a dispersion in water, water-in-oil or oil-in-water emulsion or a spray, useful for protecting plaster coatings, dispersion dyes, wall-paper, tiled surfaces, paints, glues, bitumina, furniture, leather, shower curtains, textiles, carpets, wood and paper, against a long list of pathogenic fungi, molds and bacteria. However, there is no mention of Bacteroides asaccharolyticus or gingivalis, the particular anaerobic gram negative organisms found in gingivitis. German Pat. No. 2,700,806 also discloses a mixture of the imidazolyl ketone fungicide and a quaternary ammonium bactericide useful for protecting materials such as paints, glues, bitumen, cellulose, paper, textiles, leather and wood.
Although the prior art discloses the specified imidazolyl ketone as an antimycotic agent, and its use in pharmaceutical formulations, particularly in hair and skin treating compositions, there is no disclosure of its use in dental preparations nor its effectiveness against the specific gram negative anaerobic organisms associated with gingivitis and periodontitis.